Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study

• Published in: Leukemia Vol. 33; no. 8; pp. 1996 - 2005
• Main Authors: Barbui, Tiziano, Ghirardi, Arianna, Masciulli, Arianna, Carobbio, Alessandra, Palandri, Francesca, Vianelli, Nicola, De Stefano, Valerio, Betti, Silvia, Di Veroli, Ambra, Iurlo, Alessandra, Cattaneo, Daniele, Delaini, Federica, Bonifacio, Massimiliano, Scaffidi, Luigi, Patriarca, Andrea, Rumi, Elisa, Casetti, Ilaria Carola, Stephenson, Clemency, Guglielmelli, Paola, Elli, Elena Maria, Palova, Miroslava, Bertolotti, Laura, Erez, Daniel, Gomez, Montse, Wille, Kai, Perez-Encinas, Manuel, Lunghi, Francesca, Angona, Anna, Fox, Maria Laura, Beggiato, Eloise, Benevolo, Giulia, Carli, Giuseppe, Cacciola, Rossella, McMullin, Mary Frances, Tieghi, Alessia, Recasens, Valle, Marchetti, Monia, Griesshammer, Martin, Alvarez-Larran, Alberto, Vannucchi, Alessandro Maria, Finazzi, Guido
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.08.2019
• Subjects: Antineoplastic Agents - adverse effects; Busulfan; Cancer; Cancer patients; Care and treatment; Case-Control Studies; Complications and side effects; Diagnosis; Drugs; Exposure; Health aspects; Health risk assessment; Health risks; Hematology; Humans; Hydroxyurea; Hydroxyurea - adverse effects; Interferon; Melanoma; Myeloproliferative disorders; Neoplasms; Neoplasms, Second Primary - chemically induced; Philadelphia Chromosome; Pipobroman - adverse effects; Polycythemia Vera - drug therapy; Polycythemia Vera - genetics; Primary Myelofibrosis - drug therapy; Pyrazoles - adverse effects; Risk; Risk factors; Skin cancer; Thrombocythemia, Essential - drug therapy; Thrombocythemia, Essential - genetics; Tumors
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-019-0487-8

We conducted a large international nested case-control study including 1881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n = 647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer, and melanoma) and controls (n = 1234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR = 1.06, 95% CI 0.82-1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had two-fold higher risk of non-melanoma (NM) skin cancer (OR = 2.28, 95% CI 1.15-4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR = 3.74, 95% CI 1.00-14.01), ruxolitinib (OR = 3.87, 95% CI 1.18-12.75), and for drug combination (OR = 3.47, 95% CI 1.55-7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan, and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.